8738
W. Chen, J. Xiao / Tetrahedron Letters 42 (2001) 8737–8740
Our new approach is concerned with the asymmetric
activation of conformationally flexible biphenyl scaf-
folds to give chiral phosphite ligands.10 Thus, by react-
ing the conformationally flexible, proatropisomeric
biphenyl phosphorochloridites 111 with 1 equiv. of a
chiral activator, the optically pure alcohol 2, in THF in
the presence of NEt3 at room temperature, the phos-
phites 3 could be isolated in over 90% yield (Scheme
2).12 Unlike their precursors, compounds 3aa–ae are
mixtures of diastereoisomers consisting of S-3 and R-3
(R and S refers to axial chirality). And as such, they
need not be equal molar mixtures. However, the 31P
NMR spectra of 3aa–ae obtained in CDCl3 at ambient
temperature each displayed two singlets with ca the
same intensities, which did not appear to change with
time. This observation suggests that the steric bias of
the chiral activator may not be significant enough to
distinguish the conformations adopted by the biphenyl
moiety and the two diastereoisomers of each phosphite
exist in approximately equal concentrations. A similar
JRh–P=258.5 Hz; l 120.7, JRh–P=258.8 Hz). However,
it is not clear at this stage which of the two is the more
stable. The complex [Rh(S-3ae)(R-3ae)(COD)]+, which
would be expected to give rise to two doublet doublets
or an AB multiplet in the 31P NMR spectrum, did not
appear to be formed.
Having established that the metal complexes of 3 exist
as a non-equimolar mixture in solution, we then applied
the ligands to the rhodium catalysed enantioselective
hydrogenation of dimethyl itaconate. The catalyst was
formed in situ by combining [Rh(COD)2][BF4] with 2
equiv. of a ligand in CH2Cl2. Table 1 summarises the
results obtained. As can clearly be seen, the chirally
activated biphenylphosphites are capable of face dis-
crimination and hence creating handedness in the
product. With the 3a series of ligands, all the reactions
went to completion under the conditions of substrate/
catalyst (S/C)=2000, 20°C and 12 h reaction time, with
enantioselectivities ranging from 29% to 57% ee. The ee
values for 3ae could be increased when the temperature
was lowered. Thus, ee’s rose to 68% at 0°C and 75% at
−15°C. It is not clear whether the major enantiomers of
these products are due to S-3a or R-3a coordinated
rhodium catalyst. However, if the configuration of the
hydrogenation product is determined by the axial chi-
rality of the ligands, one might expect the S configured
product to arise from S-3, as with the same reaction
catalysed by L-menthol binaphthylphosphite-Rh(I)
complexes, where (S)-binaphthyl affords the S domi-
nated enantiomer.9 The conformationally more flexible
3a ligands gave rise to higher ee values. With the 3b
series of ligands, not only were the enantioselectivities
lower but the reactions were in general slower as well.
Also, worthy of note is the observation that with some
of these ligands, the configuration of the favoured
enantiomers of the product is reversed. Thus, while 3ae
gave the S configured product with 60% ee, 3be
afforded the opposite enantiomer with 19% ee and a
much lower conversion (Table 1), indicating that the
enhanced steric bulkiness on going from 3a to 3b affects
the relative stability of the diastereoisomers of 3-Rh(I)
and/or alters the kinetic profile of each diastereoisomer
in the hydrogenation.13
observation was made with
a 2,2%-bis(diarylphos-
phino)biphenyl complex of ruthenium containing a chi-
ral activator, S,S-1,2-diphenylethylenediamine, where
two diastereoisomers of equal concentrations were
formed.4a The difference is that, in the latter case, one
of the diastereoisomers was enriched at the expense of
the other upon standing or heating for a short period of
time. We anticipated that, by placing bulky t-Bu groups
at the 3,3% and 5,5% positions of 1a, the balance between
the two diastereoisomers could be disturbed because of
increased steric interactions. This is not the case, how-
ever, as the 31P NMR spectrum of 3ba–be showed again
two singlets of ca 1:1 ratio
The balance between the two diastereoisomers of 3 did
break down upon the introduction of a rhodium com-
plex. Thus, the 1:1 mixture of S-3ae and R-3ae reacted
with half an equivalent of [Rh(COD)2][BF4] to give two
compounds in a molar ratio of 1:5, as indicated by 31P
NMR at room temperature. Only two doublets
appeared in the 31P NMR spectrum, indicating
the formation of two compounds, probably [Rh-
(S-3ae)2(COD)]+ and [Rh(R-3ae)2(COD)]+ (l 119.9,
R
R
O
R
R
O
R*OH, Et3N
THF, rt
P OR*
P Cl
+
R*OH
O
R
O
R
2a~e
R
R
3
a, R = H
1
b, R = t-Bu
HO
OH
HO
HOR* =
OH
OH
a
c
d
b
e
Scheme 2. Synthesis of chiral alcohol activated biphenylphosphites. For detailed reaction conditions, see Ref. 12.